Leukotrienes are formed by transformation of arachidonic acid into an unstable epoxide intermediate, leukotriene A.sub.4, which can be converted enzymatically by hydration to leukotriene B.sub.4 (LTB.sub.4), the structural formulae of which are represented below. ##STR2##
Recent literature suggests that LTB.sub.4 may play an important role in a variety of immunological diseases. LTB.sub.4 in vitro, is a mediator of leukocyte chemotaxis, chemokinesis, aggregation, degranulation, and superoxide generation. Administration of LTB.sub.4 induces inflammatory responses, i.e. PMN accumulation, increased vascular permeability, edema formation and hyperalgesia. LTB.sub.4 may also act synergistically with prostaglandins and other inflammatory mediators to exacerbate inflammatory, diseases. In addition, LTB.sub.4 has been detected in high concentrations in the inflammatory site in animal models and in inflammatory lesions in humans. Thus, LTB.sub.4 is thought to be a critical mediator of inflammatory, immediate hypersensitivity, renal, cardiovascular, and anphylactoid diseases and may possibly be involved in arthritis and other delayed type hypersensitivity diseases. Agents that interfere with the actions of LTB.sub.4, by blocking its action at the receptor, may have valuable therapeutic effects in treating these diseases.
By antagonizing the effects of LTB.sub.4, the compounds and pharmaceutical compositions useful in the instant invention are valuable in the reatment of diseases in which LTB.sub.4 is a factor.